Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function

Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function
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DOI:
10.1038/ncb1221
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发表时间:
2005-03-01
影响因子:
21.3
通讯作者:
Lev, S
Lev, S
中科院分区:
生物学1区
文献类型:
--
作者:
Litvak, V;Dahan, N;Lev, S

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高尔基体中甘油二酯(DAG)的水平对蛋白质转运到质膜至关重要。芽殖酵母中的研究表明,Sec 14 p,磷脂酰肌醇(PI)-转移蛋白,参与调节高尔基复合体中的DAG稳态。在这里,我们表明,Nir 2,外周高尔基体蛋白含有PI-转移域,是必不可少的维持哺乳动物细胞中的高尔基体的结构和功能的完整性。通过RNAi耗尽Nir 2导致从trans-Golgi网络到质膜的蛋白质转运的实质性抑制,并导致高尔基体中DAG水平的降低。值得注意的是,用于磷脂酰胆碱生物合成的胞嘧啶5 '-二磷酸(CDP)-胆碱途径的失活恢复了这两种作用。这些结果表明,Nir 2参与维持一个关键的DAG池在高尔基体通过调节其消费通过CDP-胆碱途径,展示了从高尔基体和脂质稳态分泌之间的接口。
The level of diacylglycerol (DAG) in the Golgi apparatus is crucial for protein transport to the plasma membrane. Studies in budding yeast indicate that Sec14p, a phosphatidylinositol ( PI)-transfer protein, is involved in regulating DAG homeostasis in the Golgi complex. Here, we show that Nir2, a peripheral Golgi protein containing a PI-transfer domain, is essential for maintaining the structural and functional integrity of the Golgi apparatus in mammalian cells. Depletion of Nir2 by RNAi leads to substantial inhibition of protein transport from the trans-Golgi network to the plasma membrane, and causes a reduction in the DAG level in the Golgi apparatus. Remarkably, inactivation of the cytosine 5'-diphosphate (CDP)-choline pathway for phosphatidylcholine biosynthesis restores both effects. These results indicate that Nir2 is involved in maintaining a critical DAG pool in the Golgi apparatus by regulating its consumption via the CDP-choline pathway, demonstrating the interface between secretion from the Golgi and lipid homeostasis.